The purpose of Fort Venango was to protect the passage from French Creek to the Allegheny River. The British intended for it to replace Fort Machault, which the French had destroyed when they retreated from the Ohio Valley in 1759.

Fort Venango was essentially a large blockhouse with earthwork defenses. It was much smaller than Fort Pitt, the primary British post in the Ohio Country. Seneca Indians attacked it during Pontiac's Rebellion in June 1763 and burned it to the ground, killing its small garrison. They forced the post's commander, Lieutenant Francis Gordon, to write down their grievances concerning the British occupation of the Ohio Country before torturing him to death. When General Amherst learned of Gordon's fate, he wrote to Colonel Henry Bouquet, "no Punishment We can Inflict is Adequate to the Crimes of those Inhumane Villains." This remark, indicative of Amherst's hatred for Indians, reflects the tone of his exchange with Bouquet about using smallpox as a weapon against them.